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Investigation of herpes simplex virus and cytomegalovirus infection in the immunocompromised host

Gor, Dehila; (1999) Investigation of herpes simplex virus and cytomegalovirus infection in the immunocompromised host. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The remit of this thesis was to examine the role of HSV and CMV infections in patients with AIDS and in bone marrow transplant recipients. PCR was used to monitor the efficacy of a novel drug, valaciclovir, in ADDS patients at risk of CMV disease. Valaciclovir was found to be effective at reducing the excretion of CMV in patients who were baseline PCR-positive, and in patients with advanced HIV disease, the drug delayed the onset of CMV end-organ disease. A confirmatory assay based on an oligonucleotide probe conjugated to alkaline phosphatase was used to evaluate a number of samples from the ACTG 204 study that produced non-specific results using PCR. Quantitative PCR was used to retrospectively monitor fluctuations in viral load in the blood of BMT recipients. When the relative contribution to CMV disease of risk factors such as recipient CMV serostatus, virus load, T-cell depletion, and acute-GvHD was assessed, virus load was found to be the most significant risk factor for disease. In univariate statistical analysis, recipient seropositivity was also identified as a significant risk factor for CMV disease. Immune modulation and the dynamics of virus clearance from the blood were assessed in order investigate the efficacy of antiviral intervention with ganciclovir. Finally, nine herpes simplex vims isolates from 3 HIV patients and one BMT patient, which were resistant to ACV in vitro, were subjected to phenotypic and genotypic analyses. All the viruses were found to be TK deficient, and genotypic analysis showed the presence of a number of mutations including single base deletions and coding substitutions.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigation of herpes simplex virus and cytomegalovirus infection in the immunocompromised host
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences; Transplant recipients
URI: https://discovery.ucl.ac.uk/id/eprint/10114968
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